LV10314B - Process for preparation of macrolides - Google Patents
Process for preparation of macrolides Download PDFInfo
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- LV10314B LV10314B LVP-93-1406A LV931406A LV10314B LV 10314 B LV10314 B LV 10314B LV 931406 A LV931406 A LV 931406A LV 10314 B LV10314 B LV 10314B
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/238—Cyclohexane rings substituted by two guanidine radicals, e.g. streptomycins
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/181—Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/465—Streptomyces
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
LV 10314
CnOCOE ΠΟΠΥΗΕΗΜΗ MAKPOLļl1KJlMHECKMX COEflMHEHMfi
OnMCAHME
HacTOHLuee Μ3θ6ρβτβΗΜβ othocmtch k cnoco6y ποπυμθημλ ηοβμχ οοθπμηθημμ 3ητμ6μοτμκ3. B 3aaBKe Ha Bbiflawy naTeHTa Benmo6pmaHm N 8522699 onMcaHO nonyHeHne 8ητμ6μοτμκοβ S 541, KOTopbie mojkho BbipenuTb M3 npopyKTOB φθρΜβΗτβΜΜΜ BHfla Streptomyces. Ahtm6motmkm S 541 npeflCTaBnMJOT co6oii rpynny οοθαμηθημμ, μμθκ>ιιιμχ HenonHyK> $opMyny (1)
QH
Ι/lTaK, xax onucaHO b naHHOM onMcaHMM, BbmBneHa pononHMTenbHaM rpynna coeflHHeHMM, o6nanaioiHMX 3ητμ6μοτμηθοκομ aKTMBHOCTbio, KOTopbie mo>kho nonyHMTb noepeflCTBOM ΧΜΜΜΗβΟΚΟΜ ΜΟβΜφΜΚΒΜΜΜ aHTMČMOTMKOB S 541 ΜΠΜ nyieM BbipeneHMa nx m xynbTypbi MMKpoopraHM3MOB popa Streptomyces.
HoBbie coeflMHeHM3 npepnaraeMoro Μ3θβρβτβΗΜΜ oSnapaioT amrMo6MTMHecKOM aKTMBHOCTbK) μ/ ΜΠΜ ΠρΜΜβΗΜΚΠΌΜ KŪK npOMe>KyTOHHbie npOflyKTbl npn ΠΟίψΗβΗΜΜ ppymx aKTMBHbix οοθαμηθημμ μ/ μπμ npn BbipeneHnn μπμ οημοτκθ οοθαμηθημμ aHTMČMOTMKOB S 541. %
CoepMHeHMfl HacToamero Μ3θδρβτβΗΜΜ npepciaB/iaiOT co6oii 23-peoKCM, h 23-rnnpoKcnn μπμ 3aMeipeHHbix ruppoKCunbHbie aHanoru 3ητμ6μοτμκοβ S 541, KOTopbie μμθιοτ ™ppoKcmibHyK) μπμ 3aMemeHHyio rnflpoKCMJibHyio μπμ 3aMemeHHyio rnnpoKcnnbHyio rpynny b ποπο>κθημμ 5.
TaKMM o6pa30M, HacTonmMM Μ3οβρβτβΗΜβΜ npepnaraeTca, b ηβοτηοοτμ, coeflHHeHMM φopMynbι (2), 2
rne R1 πρβηοτβΒΠΛβτ MeTMnbHyio, 3TMnbHyio μπμ M3onponnnbHyio rpynny: R2 m r3 npeflCTaBnHHDT aTOM Bonopona, m OR4 npepciaBnaioT rnflpoKCnnbHyio rpynny, μθτοκομ, anKaHomioKCM rpynny, MMeK>myio C-j-Cg a/iKMnbHbiM φροΓΜβΗΤ, Heo6a3aTenbHO 3aMemeHHbiii $eHOKcnrpynnoii μπμ rpynny OCOO R5, rne R5-C-|-Cg anKun.
KaK yKa3biBanocb paHee, οοθαμηθημπ npennaraeMoro Μ3θβρβτβΗΜΠ MoryT ΠΡΜΜΘΗΒΤΟΒ B Κ3ΗΘ0ΤΒβ aHTMČMOTMKOB Μ/ ΜΠΜ KaK npOMe>KyTOHHbie COeflMHeHMfl flna nonyHeHMH npyrnx aKTMBHbix οοθαμηθημμ μ/ μπμ npn BbineneHMM μ οημοτκθ COeflMHeHMM aHTH6MOTMKOB. S 541 .B tom cnynae, Korna npennaraeMbie coeflMHeHMH πρμχοαμτοπ ncnonb30Baib KaK nonynpoflyKTbi, R2 μ/μπμ -OR4 Moryr 6biTb 3amMiueHHbiMM rnflpoKcnnbHbiMM rpynnaMM. Rcho, hto TaKaa rpynna non>KHa μμθτβ MMHMManbHoe KoniinecTBO nonojiHMTenbHbix cpyHKMMOHajibHbix rpynn, htoSbi M36ex<aTb flononHMTenbHbix peaKUMOHHbix ueneii m non>KHa 6biTb TaKoea, HTo6bi CTano βο3μο>κηβιμ M36MpaTenbHo BoccTaHaB/iMBaTb M3 Hee rnflpoKCnnbHyK) rpynny. ripuMepbi 3amnTHbix mppoKcnjibHbix rpynn M3BecTHbi m onncaHbi, HanpMMep, b MOHorpa0MM ” 3ammHbie rpynnbi b opraHMnecKOM ομητθ3θ” (Protective groups .in Organic Sinthesis." by Theodora W.greene, Weley Interscience, NewYork, 1981) m 3amnTHbie rpynnbi b opraHMnecKOM χμμμμ ” (Protective groups in Organic Chemistry "by J.F.W. Me Omie Plenum Press, London,1973). 3aaBneHHbie οοθαμηθημπ o6nana»OT aHTMČMOTMHecKofi aKTMBHOCTbK), HanpMMep, aHTMrenbMMHTHOM aKTMBHOCTbK), HanpMMep, ΠρΟΤΜΒ HeMaTOflOB, M B MaCTHOCTM aHTM-3HR0napa3MTapH0M M aHTM- 3KT0napa3MTapH0M aKTMBHOCTbK). 3KTonapa3MTbi m 3Hflonapa3MTbi 3apaxaiOT nrofleii m uenbīii pnn >KMBOTHbix m ocoSeHHo ΜΜβιοτ ujMpoKoe pacnpocTpaHeHMe cpeflM cenbCK0X03HMCTBeHHbix >KMBOTHblX Τ3ΚΜΧ KaK CBMHeM, OBeLļ, KpynHOrO poraTOrO CKOT3, K03 M flOMam-ηθμ nTMLļbi, noujafleM m flOMauiHMX χμβοτηβιχ, HanpMMep, coāaK μ κοίϋβκ. napa3MTapHaa ΜΗφβκι^ΜΗ flOMaiuHero CKOTa, npMBOflnman κ οηθμμμ, HeflOCTa- 3 LV 10314 TOHHOCTM ΠΜΤβΗΜΗ Μ ΠΟΤβρΜ ΒΘΟβ, ΛΒΠΛΘΤΟΛ OCHOBHOM ΠρΜΗΜΗΟΜ 9Κ0Η0ΜΜΗβ0-ΚΜΧ nOTepb BO BC6M ΜΜρβ . K npeflCTaBmenflM 9Hflonapa3HTOB, 3apaxcaioinMx yKa3aHHbix χμβοτημχ μ/ μπμ ΠΚ3ΑΘΜ 0TH0C3TCH AncvIostoma.Ascarida. Ascaris. Aspicularis. Bruaia. Bunostomum. Capillaria. Chabertia. Cooperia. Dictvocaulus. Dirofilaria. Dracuculus. Enterobius. Haemonchus. Heterahis. Loa. Necator. Nematodirus. Nematospiroides (Helioomoroides. Nipppstronavlus. Oesophaaostpmum. Onchaceroa. Ostertaaia. Oxiuris.Parascaris.Stronavlus.Stronavlpides.Svphacia.Toxascaris.Toxocara. Irichonema. Irichostronavlus. Irichinella. Irichuris. Uncinaria n Wucharecia. npuMepaMM 3KT0napa3MT0B, 3apax<aiOLHMX χμβοτημχ μ/ μπμ niofleii hb-πηιοτοη ηπθημοτοηογμθ 3KTonapa3MTbi, HanpMMep, χοπηιιΐΜβ HaceKOMbie, naflanbHan Myxa,6noxM, bujm, Knemu, cocymne HaceKOMbie, μοκοαοβμθ ieņemu m npyrne flByKpbinbie HaceKOMbie - Bpe/jmenM. K npHMepaM TaKoro pona 3KTonapa3MTOB, 3apax<aioinMX >κμβοτημχ μ/μπμ πιοριβίί οτΗοοητοη Ambylomma, Boophilus, Chorioptes, Culliphore, Demodex, Demallenia, Dermatobia, Gastrophilus, Haematobia, Haematopinus, Haemophysalis, Hyalomma, Hyperderma, lxodes, Linognathus, Lucilia, Melophagus, Oestrus, Otobius, Otodectes, Psoregates, Psoroptes, Rhipicephalus, Sarcoptes, Stomoxys, m Tabanus. 06Hapy>KeHO) hto npepnaraeMbie οοθαμηθημη θφφβκτΜΒΗΟ neMCTByiOT xax in vitro, Tax m in vivo προτΜΒ uiMpoKoro pana 9Hnonapa3MTOB m 9KT0napa3MT0B . B HacTHOCTM, o6Hapy5KeHO, hto οοθαμηθημη HacTonmero Μ3θ6ρβτβΗΜ* 3κτμβηο AetiCTByiOT προτΜΒ ΗβΜβτοηοΒ TaKMX Kax Haemonchus contortus, Ostertagia cireumeineta, lrichostrongylus, colubiformis, Dictyocaulus, viviparis, Cooperia, oncophera, Ostertagia, ostertagi, Nematospiroides dubius h Nippostrongylus braziliensis m napa3MTapHbix κnemeti, KaK HanpMMep Sarcoptes m Psoroptes sp.
TaKHM o6pa30M, npennaraeMbie οοθαμηθημη HaxojqnT πρΜΜβΗβΗΜβ npH neneHHM χμβοτηηχ m moneii c 9Hflonapa3mapHoii m/mam 9KTonapa3MTapHOM ΜΗφβΚΜΜΗΜΜ. BHflbl napa3MT0B MeHflIOTCfl B COOTBeTCTBMM C Χ03ΗΜΗ0Μ (>KMBOTHblM) H noMMHnpyioinnM MecTOHaxo>KfleHneM ΜΗφβκΜΜΜ . CneflOBaTenbHO, HanpMMep, B036yflMTenM Haemonchus contortus, Ostertagia cireumeineta m Trichostrongylus culubiformis oābiHHO nopaaeaiOT οβθμ m npeMMymecTBeHHO noKanM3ytOTca b x<enyflKe μ τοηκομ ΚΜΐιικβ, b to BpeMa xax Dictyocaulus viviparus, Cooperia oncophora, m Ostertagia osteryagi obbiHHO nopaaeaioT KpynHbiM poraTbiii ckot m noKanM30BaHbi, maBHbiM o6pa30M b πθγκμχ, κμιιιθηημκθ μπμ xenyflKe, ΟΟΟΤΒΘΤΟΤΒβΗΗΟ. AHTMbMOTMHecKan aKTMBHOCTb npennaraeMbix οοθαμηθημμ μο>κθτ 6biTb 4 nponeMOHCTpupoBaHa, HanpMMep, CBoeii aKTMBHOCTbio in vitro προτΜΒ οβο6οαηο )KMByiiinx ΗθΜβτοηοΒ, HanpMMep, Caenorhabiditis elegans.
KpoMe Toro, 3a«BneHHbie οοθαμηθημα μμθκ3τ πρμμθηθημθ b KanecTBe npoTMBorpn6KOBbix BemecTB, HanpMMep, npcmiB LUTaMMOB Candida, xax HanpMMep, Candida albicans m Candida glabrata μ προτΜΒ προχοκβίί, TaKMX xax Saceharomces carlsbergensis. Οοθπμηθημλ HacTOfuuero Μ3θ6ρβτβΗΜΑ κροΜβ τογο μμθκϊτ πρμμθηθημθ β 6opb6e c BpepnTenaMii-HaceKOMbiMM, KnemaMM μ HeMaTonaMu β cenbCKOM χο33μοτβθ, caflOBOflCTBe, necoBopcTBe, 3flpaB00xpaHeHMM m xpaHeHMM προργκτοΒ. Mmm mojkho ycneiuHO o6pa6aTbiBaTb BpenmeneM ποηβν m cenbCKO-χο3ημοτβθηημχ KynbTyp, βκπJonas xne6Hbie 3naxn (HanpMMep, niueHkiuy, HHMeHb, Mauc, PMC), OBOllļM (HanpMMep, COK)), C{)pyKTbl (ΗβΠρΜΜβρ, ίΐβΠΟΚΜ, ΒΜΗΟφβΑ M i4MTpycoBbie), Hap«py c KopHennojgaMM (HanpMMep, caxapHyio CBeKny, κβρτοφθπ^. XapaKTepHbiMii npuMepaMM Taxnx BpepMTeneM ηβπαιοτο5ι 0pyKTOBbie KneiUM μ τπα, HanpMMep, Aphistabae, Nulacorthum circumflexum, Muzus Nersicae, Nephotexttix cineticeps, nilparvata Lugens, Panonychus almi, Phorodon humuli, Phyllocoptruta oleivora, Tetranychys urtucal m npepcTaBMTenM popaTrialcuroides; HeMaTOflbi, HanpMMep,npemcTaBMTenM popa Aphelencoides, Globodera, Heterodera, Meloidogyne m Panagrellus; HeiuyM4aTbie, HanpMMep, Heliothis, Plutella m Spodoptera; ponroHOCMK-KanaHnpMHa, KaK, HanpMMep, Anthonomus grandīs m Sitophilus granarius; xpymaKM MyHHbie, HanpMMep,Tribolium castaneum MyxM, HanpMMep, Muscaolomestica; MypaBbM pMXTepa; μοπμ-μμηθρμ y3K0Kpbinbie; Pearpsilla; TpMncbi Ta6aHHbie; TapaKaHOBbie, HanpMMep, Blatella germanica m Periplaneta MocKMHbie, xax HanpMMep, Aedes aegypti. B COOTBeTCTBMM C HaCTOfllJļMM Μ3θ6ρβΤβΗΜβΜ npeflHOJKeHbl COeflMHeHMfl $opMynbi (2), Kax yKa3biBanocb Bbiuie, KOTopbie Moryr 6biTb Mcnonb30BaHbi β KanecTBe 3ητμ6μοτμκοβ . B nacTHOCTM, mx mojkho Mcnonb30BaTb πρΜ πθηθημμ χμβοτηβιχ m mopeM, nopa>KeHHbix 3Hponapa3MTapHOM μ/μπμ φμ6κοβομ ΜΗφβΚΜΜΛΜΜ Μ Β ΚΒΗβΟΤΒβ neCTMLļMflOB ΡΠ3 ČOpbČbl C ΒρβρΜΤβΠΛΜΜ-ΗΒΟβΚΟ-MblMM, KJiepaMM M HeMaTOpaMM B cenbCKOM X03BMCTBe, CapOBOflCTBe, ΜΠΜ neCHOM X03BMCTBe. Mx MOJKHO npMMeHflTb, ΚρΟΜβ ΤΟΓΟ, ObblHHO Β ΚΒΗβΟΤΒβ necTMMMflOB b flpyrMX o6cTaaTenbCTBax, HanpMMep, b xpaHMnMLuax,3flaHMax μπμ ppyrMX o6iqecTBeHHbix Meciax μπμ MecTax noKanM3auMM cenbCKOxo-3JiMCTBeHHbix BpeflMTeneM. no-cymecTBy npepnaraeMbie οοθαμηθημα Moryr 6blTb ΠρΜΜβΗβΗΜ ΠΜ6θ K X03flMHy ()KMBOTHOMy ΜΠΜ ΗβΠΟΒβ^,ΠΜβΟ K KynbiypHblM pacTeHMHM μπμ ppyroM pacTMTe/ibHOCTM), πμ6ο k caMMM BpepMTeniiM μπμ Meciry mx pacnonojKeHMjR. 3asiBneHHbie οοθαμηθημη Moryr 6biTb cφopMyπMpOBaHbι prm npneMa 5 LV 10314 B πιοδοM yno6HOM φθρΜβ ΠρΜ MCn0nb30BaHMM B ΒβΤβρΜΗβρΜΜ ΜΠΜ npaKTMHeC-κοιί μθρμμμηθ . TaKMM o6pa30M, HacTOflujee Μ3θ6ρβτβΗΜβ copep^KUT b npepenax οβοθγο oāteMa $apMaLļeBTHHecKne κομπο3μμμμ, copep^amne οοθρμηθημθ cornacHO 3ajiBneHH0My Μ3θδρβτβΗΜΐο, npuroflHoe ρππ πρμμθηθημλ b BeTepMHapMM μπμ Tepannn . TaKne κομπο3μμμμ MoryT 6biTb npepcTaBneHbi npn Mcnonb30BaHMM b TpaflMLļMOHHOM φθρΜβ C nOMOLLļbK) OflHOrO Unu HeCKOnbKMX n0flX0flJUUMX ΗΟΟΜΤβΠβΜ μπμ HanonHMTeneii. npepnaraeMbie κομπο3μμμμ οορβρχοτ cociaBbi b φορΜΘ, ocoāeHHO npuroflHoti pna napam-epanbHoro (b tom ημοπθ, ββθρθημθ BHyTpb μοποηηομ >Kene3bi), opanbHoro, peKTanbHoro, μθοτηογο πρΜΜβΗβΗΜπ b βμαθ MMnnaHTama, ρππ πρμμθηθημπ npn ma3Hbix, yuiHbix μπμ 3a6oneBaHMnx ΜΟΗΘΠΟΠΟΒΟΜ CMCTeMbl. ΠΟΡΧΟΡΛΙΜΜΜΜ Cn0C06aMM M areHTaMM ΡΠΠ ΠρΜΓΟΤΟΒΠβΗΜΠ cocTaBa οοθαμηθημμ HacTonmero Μ3ο6ρβτβΗΜΠ, πρμγοαηογο ρππ Mcnonb30BaHMa b BeiepMHapuM μπμ Tepannu, πβππκπόπ cnocočbi, KOTopbie oniicaHbi b πβτβΗτβ ΙΟ>κηομ ΑφρΜΚΜ N 85/7049 prm οοθαμηθημμ βητμ6μοτμκοβ S 541.
3aflBneHHbie οοθαμηθημπ mo>kho npMMeHaTb b κομ6μηβμμμ c npyrnMM φβρΜβΜΘΒΤΜΗΘΟΚΜ aKTMBHbIMM ΜΗφΜΑΜβΗΤΒΜΜ.
CyMMapHaji cyTOHHan po3a npe/yiaraeMbix οοθαμηθημμ, npMMeHneMan kūk b BeTepnHapnn, TaK m b Tepannn,āyfleT οοοτβθτοτβθηηο b MHTepBane 1-2000 μγ/κγ Beca Teņa, npeflnoHTMTenbHO 50-1000 μγ/κγ, πρμηθμ yKa3aHHbie fl03npoBKn mo>kho npMHMMaTb b npo6Hbix no3ax, HanpMMep, 1-4 pa3a b neHb. 3a^BneHHbie οοθαμηθημπ mo>kho cocTaBnm b πιοδοίί ypo6HOM φορΜβ, npuroflHoii pna 3eMnepenn3 μπμ caflOBOflCTBa. TaKMM o6pa30M, HacTonmee μ3ο6ρθτθημθ BKJiiOHaeT b npepenax ceoero o6teMa cociaBbi, conepaomMe coeflMHeHM3, npeflHa3HaHeHHoe πππ πρμμθηθημη b 3θμπθαθπμμ μπμ caflo-βοαοτβθ. TaKMe peMemypbi ΒκπιοΗβιοτ cyxMe μπμ >κμηκμθ φορΜΜ, HanpMMep, piycTbi, BKnioHan nbineBMflHbie cy6cTpaTbi μπμ KOHuempaTbi, nopouiKM, b tom ημοπθ pacTBopMMbie μπμ CMaHMBaeMbie ποροιυκΜ, rpaHynbi, BKnronan MMKporpaHynw m AMcneprMpyeMbie rpaHynbi, τβδπβτκΜ, TeKynMe BemecTBa, 9MynbCMM, HanpMMep, pa36aBneHHbie 9MynbCMM μπμ 9MynbrMpyeMbie κοηρθητρβτβι, nponMTOHHbie COCTaBbl, HanpMMep, COCTaBbl flHfl ηρΟΠΜΤΚΜ ΚΟρΗβίί Μ ΟβΜΠΗ, ΠρθΤρ3ΒΠΜΒ3ΤβΠΜ οθμπη, ceMeHHbie rpaHynbi, MacnnHbie KOHuempaTbi.MacnnHbie pacTBopbi, MHteKUMM, HanpMMep, MHbeKLļMM B ΟΤΒΟΠ, paCTBOpbl flnn OnpblCKMBaHMH, flblMbl M TyMaHbi. ΠορχοηπιιΐΜβ cnoco6bi m areHTbi pnn cocTaBneHMn peL|enTypbi npeflnaraeMblX ΟΟβΑΜΗβΗΜΜ ΡΠΠ πρΜΜβΗβΗΜΠ B CapOBOflCTBe ΜΠΜ 3βΜΠβΑβΠΜΜ ΒΚΠΙ0Η3Κ)Τ Τβ, KOTopbie paCKpbITbl B ΠβΤβΗΤβ IO>KHOM ΑφρΜΚΜ N 85/7049 ρππ aHTMČMOTMKOB S 541. 6 npn οοοτββπθημμ peuenTypbi, KOHueHTpauMn θκτμβηογο BeipecTBa očbiHHO cocTaBnaeT οτ 0,01 po 99 Macc.% m 6onee npepnoHTMTenbHO ot 0,01- 40 Macc.%. npoMbimneHHbie (ToeapHbie) npopyKTbi o6biMHO npMroTOBneHbi b BMpe KOHLļeHTpMpOBaHHblX Κ0ΜΠ03ΜΜΜΜ, KOTOpbie npM MCnonb30BaHMM pa36aBn«IOT flO Tpe6yeMoii KOHLieHTpapMM, HanpMMep, ot 0,001 po 0,0001 Macc. %. flpu MCn0nb30BaHWM B ΒβΤθρΜΗθρΜΜ ΜΠΜ B CapOBORCTBe Μ 3βΜΠβρβΠΜΜ, m b cnyHae, Korpa npepnaraeMbie coepMHeHMn πβππιοτοπ npopyicraMM, opa3yeMbiMM nocpepcTBOM φβρΜβΗΤθρΜΜ, >KenaTenbHO Mcnonb30BaTb eecb OpopunbHbiiĪ 6ynbOH b «anecTBe μοτοηημιο θκτμβημχ οοθρμηθημμ. KpoMe ΤΟΓΟ, ΜΟ>ΚΘΤ 6blTb npurOPHblM MCnonb30BaHMe 0βΘ3Β0>ΚβΗΗ0Γ0 6ynbOHa (copeparamero μμμθπμμ) μπμ μμρθπμπ, οτρθπθηηογο Μ3 6ynbOHa μ nacTepn30BaHHoro, μπμ 6onee npepnoHTMTenbHO BbicyujeHHoro. ripu acenaHMM, y«a3aHHbiM 6ynbOH μπμ MnpenuPi MoryT 6biTb οφορΜγπΜροΒθΗΗ β κομπο3μρμμ, xaK yKa3biBanocb Bbiiue, BKniOHaioiUMe Tpapminom-ibie nHepTHbie ηοομτθπμ, η3Π0πημτθπμ μπμ pa36aBMTenM. Αητμ6μοτμηθοκμθ οοθρμηθημπ npepnaraeMoro Μ3ο6ρθτθημμ Moiyr BBOPMTbCn M npMMeHHTbCn Β Κ0Μ6ΜΗ314ΜΜ C ρργΓΜΜΜ aKTMBHbIMM ΜΗφΜΡΜβΗΤΘΜΜ. Β HacTHOCTM, npepnaraeMbie οοθρμηθημπ θητμΟμοτμκθ Moryr “ Mcnonb30BaTbcn ΒΜβοτβ c οοθρμηθημπμμ 3ητμ6μοτμκοβ S 541 μπμ c ppyrMMM 3ΗΤΜ6Μ0ΤΜΗβ0ΚΜΜΜ ΟΟβΡΜΗβΗΜΠΜΜ ΗβΟΤΟΠίρβΓΟ Μ3θ6ρβΤβΗΜΠ. ΘΤΟ ΜΟ)ΚβΤ B03HMKHyTb, HanpMMep, β cnywae, Korpa HeonMmeHHbie npopyKTbi βρωκβΗΜπ B3aMM0peiicTByioT cornacHO cnoco6y HacTonmero Μ3θ6ρβτβΗΜπ 6e3 npepiuecByKDmero μπμ nocnepyiomero οτρβπβΗΜπ; yKa3aHHoe Μωκβτ 6biTb npepnOHTMTenbHbIM, HanpMMep, npM Μ0Π0ΠΒ30Β3ΗΜΜ ΟΟβρΜΗβΗΜΜ Β 3βΜΠβρβΠΜΜ, rpe Ba>KHO o6ecneHMTb (coxpaHMTb) HM3Kyio ce6ecTOMMOCTb προργκρΜΜ. 1. AKTMBHOCTb προτΜΒ Nematospiroides dubius
Bbina onpepeneHa peiicTBeHHOCTb οοθρμηθημμ HacTonmero ΜβοδρβτβΗΜΠ προτΜΒ Nematospiroides dubius. KOTopbiM μηΦμρμροβθπμ MbiuieM. CaMKy μηιιιμ CR/H (18-22 r) 3aoa3MnM πμημηιομμ 100 L3 larvaed N dubius μ ΜΗφθκρΜΜ panu pa3BMTbcn nonHOCTbio (oObNHO 3 HepenM). 3aieM MbiLUb ofipačOTanM πγτβΜ epMHopa30Boro CTOMaTMHecKoro npMeMa οοθρμηθημπ HacTonmero Μ3ο6ρβτβΗΜΠ b P03Mp0BKe 3/4 TMTpOBaHHOM P03bl. ΟθβΡΜΗβΗΜΠ ΒΒΟΡΜΠΜ Β ΠρΟΠΜΠβΗ ΓΠΜΚΟΠβ. 3aieM MbiLUb BbipepaonM no KpaMHeii Mepe 3 ρηπ (o6bNHO 5 ρΗβίί) ρππ τογο,ητο6η y6MTb ΜΗφβκρΜίο β Μβοτβ ee pa3BMTMn, μ τοΗκγιο ΚΜΐιικγ ypanMnM. Bbipe3aHHyio HaCTb KMLUKM pa3pe3anM HO>KHMl4aMM C TynblMM KOHLjaMM ρππ ΤΟΓΟ, HTOObl 0CB060PMTb OT KMLUeHHOM 0ΠΜ3Μ. 3penbie mMCTbl COOpanM nocpepcTBOM 7 LV 10314 MOflMCpMLļMpoBaHHoro annapaia Baarmann'a. BpeMH MHrpapHH cocTaBrmno 5 nacoB h b τθηθημμ 9Τ0Γ0 nepnopa MnrpnpyioiiiMe mucTbi dbinn npn TeMnepaType 37°C, κοτοργιο noppepacHBanM. CnycTa 5 nacoB HeiinoHOByK) ceTicy, nepe3 KOTopyio MnrpnpoBann γπηοτμ, npoeepunn c noMombfo nynbi, c υβθπμμθημθμ b 2 pa3a. TnHCTbi, coSpaHHbie Ha οβτκβ, η MHrnpoBaBuiHe nopcHHTanH ρπ« nonyHeHHfl očiuero KonunecTBa γπηοτοβ pjih Kalpoti muujm, m cpaBHunu c KomponbHoii rpynnoii.
Cnepya Θτοίί Μβτορπκβ, 6bmo HaHpeHo, hto npn po3e coepHHeHMM HacToamero μ3ο6ρθτθημλ 10 μγ/κγ o6mee κοπμηθοτβο γπηοτοβ ρππ o6pa6oiaHHO ίί MbiuiM 3HaHmenbH0 yMeHbiuMnocb.HanpMMep, οοθημηθημθ npHMepa 3 npneeno κ yM6HbUJ6HMlO ΓΠΗΟΤΟΒ B ΠρΟΡβΗΤΗΟΜ ΟΤΗΟΙΙΙβΗΗΗ 06pa60TaHHblX MblUJeK K KOHTpOnbHbIM 6θΠΘΘ ΗΘΜ Ha 80%.
2. AKTMBHOCTb ΠΡΟΤΗΒ ΜΗΟΓΌθ6Ρ83Μ51 9KT0- M 3H£10naPa3HT0B ΠΠΠ Pa3nHHHblX ΒΗΠΟΒ ?KHBOTHblX а) EpMHCTBeHHaa po3a (800 μγ/κγ οοβρΗΗβΗΜΠ npHMepa 3 npHH5rran βη^ρμβθηηο ηπη BBepeHHaH πορκωκΗΟ, nonHOCTbio ycTpaHana mncTbi y τβππτ, 3apax<eHHbix γπηοτομ Cooperia oncophera. б) B ΤΘΜΘΗΜΘ 5-ρΗβΒΗΟΗ 06pa60TKM ΚρΟΠΜΚΟΒ, 3apa>KeHHblX ΠΗΗΗΗΚ3ΜΗ Phipicephalus appendiculolus c noMombK) coepHHeHHa npHMepa 3 3th ΠΗΗΗΗΚΗ yHHHTO>KariMCb Ha 97%. c) npopyKT npHMepa 3 προπΒππ a6conioTHyK) θφφβκτΗΒΗΟΟΤΒ, Korpa ero CTOMaTMHecKM b po3e 200 μγ/κγ ββθπη noiuapnM, ηηΦημηροβθηημμ Parascaris. d) npopyKT npHMepa 3 6bin 3φφβκτΜΒβΗ TaK >κβ, kūk Μβθρμθκτμη, Korpa ero BBORHnH CTOMaTMHecKM C P030H 200 ΜΓ/ΚΓ, ΓφΟΤΜΒ ΠΗΗΗΗΟΚ Μ Bbl3peBUJHX Nematofirus bottus m B3pocnbix Ostertagia circumeineta.Jrichostronavlus axci.Haemonchus contortus. Nematodirus spathiaer.Cooperia curtucci h Trichostronavlus vitrinus. e) npopyKT npHMepa 3 6bin adconfOTHO θφφβκτπΒβΗ, Korpa ero ββορηπη b P03e 150 μγ/κγ cočaKaM, ηηΦηρηροβρηημμ Toxocara. a) CoepHHeHHe.npHMepa 3, BBepeHHoe πορκο>κηο, προπΒππο 3φφβκτπΒΗθοπ> Ha > 98% προτπΒ Oesophaaostomum. KOTOpbiM dbinn 3apa>KeHbi CBHHbH. δ
OueHKa neMCTBMn 23-De30Kcn OaKTODa A (Πρμμθρ 3Ϊ Ha ΜΗΟθκτΜϋΜΠΗνκρ aKTMBHOCTb.
Bce KOHueHTpaMMM, KOTopbie 3jqecb πρμβθρθημ, paHbi no otholuohmio k aKTUBHbiM MHrpnflneHTaM. OnbīTHbie pacTBopbi 6binn npnroTOBneHbi πγτβΜ pacTBopeHMH aKTMBHoro nHrpnpneHTa b 35% pacTBope apeTOHa c bopom b KOHLļeHTpaunn 1000 nacTen Ha μμπμοη, 3Θτθμ pa36aBneHbi bopom, ecnn 3to ηθο6χορμμο. Tetranychus urtical ( P. npaMoe οοπροτμβπθημθ) 2-o6o3HaHeH-HbiM nayKOo6pa3HbiM κπθιρθμ.
Bbinn OTo6paHbi csoKeHLJībi 6ο6οβμχ pacTeHMM, KOTopbie, pa3BMBancb Ροοτμγπμ 7-8 cm, mx cpe3anM, TaK, hto b KaxflOM ropujKe ocTanocb no opHOMy pacTeHHio. Ot nMCTOMKa, BbiČpaHHoro M3 βοθμ rpynnbi pacTeHMM OTpe3ann ManeHbKMH KyconeK μ πομθοτμπμ Ha KeoKflbiii hmctok McnbrryeMoro pacTeHMn. 3to cpenanH 3a pea waca no o6pa6oTKn, HToObi no3BonMTb KneipaM nepepenraTbcn κ ncnbiTyeMbiM pacTeHMHM m oTKnapbieaTb Ha hmx ama. Pa3Mep cpe3aHHoro KycoMKa μ3μθηπθτοη, mo6bi nonyHMTb οκοπο 100 κπθιμθμ Ha hmct.
Bo BpeMH o6pa6oTKM KycoweK nMCTa, Mcnonb3yeMoro pnn nepeHOca Knemeii, ypanaeTcn h Bbi6pacbiBaeTcn.He6onbman ponn 3apaxeHHbix pacTeHMM norpy>xaeTcn b οπμτημμ pacTBop Ha 3 ceKyHpbi c πθρθμθιιιμβθημθμ m BbiflepjKMBaeTcn nop KonnanKOM pnn BbicyujMBaHnn. Ρθογθημπ Bbipep>KMBaK>T b ΤΘΗΘΗΜΘ 2-Χ ΡΗΘΜ, ΠρθΧφθ ΗΘΜ penaiOT OLļeHKy KOnHHeCTBa yHHHTO>KeHHblX 3penbix napa3moB, ncnonb3yn ρππ κοΗτροππ nepBbiii hmctok. ΒτοροΡί hmctok Bbipep>KMBaK)T Ha pacTeHMM ppyrne 5 ρηθμ, npe^pe ηθμ penaiOT HačntopeHMH 3a ΠΟΓΜβίυΜΜΜ HMLļaMM M/ΜΠΜ BHOBb nOHBHBLUMMMCH ΠΜΗΜΗΚ3ΜΜ HaCeKOMblX.
Empoasea abrupta. 3penbie 6ποιιικμ Ha nncTbnx κβρτοφθππ ΠμΟΤΟΗΘΚ 6ο60ΒΟΓΟ paCTeHMH, ΠΜΜφΟΚΟΜ φθΟΟΠΜ ΡΠΜΗΟΜ 5 CM, OKyHynM β onbīTHbiii pacTBop Ha 3 ceKyHpbi npn nepeMeuiHBaHHH μ πομθοτμπμ nop KonnanoK, ητο6ν BbicymnTb. Πμοτοκ πομθοτμπμ b HaiUKy ΠβτρΜ 10χ10 mm, copep>Kamyfo Ha ρβθ Bna>KHyK) φΜΠΒτροΒ3ΗΗνιο 6yMary. B Ka>Kpyio HauiKy πομθοτμπμ οκοπο 10 3penbix πμογβθηηβιχ δποιυβκ μ προβθπμ o6pa6oTKy β τθηθημθ 3-Χ ΡΗΘΜ πρθ>κρθ ΗΘΜ cpenanH ΠΟΡΟΗΘΤ ΠΟΓΗβιυΜΧ HaCeKOMblX.
Heliothis virescens
ΟβΜπροπΜ xnonKa OKyHynM b onbīTHbiii pacTBop m BbicyujMnM nop KonnaHKOM.riocne cyiiiKM Kaxpyto H3 hmx pa3pe3ann Ha ηθτβθρμηκη h pecmb ηθοτθμ πομθοτμπμ OTpenbHO β μθρμρμηοκμθ nnacTMaccoBbie naiiJKM ο6τ>θμομ 30 μπ, copepacaujMe KycoHKM Bnax<Hbix 3y6oBpane6Hbix τθμποηοβ ρπμηομ 5-7 mm. OpHy TpeTbK) nacTb ryceHMp βηθοπμ b Kaxpyio naujKy m noKpbinM KapTOHHbiM 9 LV 10314
KonnaKOM.06pa6oTKy npoBOflnnn b τθηθημθ 3-χ πηθμ, a nocne 9τογο noncMmanu HMcno πογμ6ιιιμχ n yMeHbiueHMe nopunM ποβρθ>καθημμ. LLlKana ομθηκμ 0 = ηθτ Θφφβκτβ 3 = 36-45% πογμ6ιιιμχ 1 = 10-25 %norn6uJMX 4 = 46-55% ποπιβιΐίΜΧ 2 = 26-35% norw6mnx 5 = 56-65% πογμ6ιιιμχ 6 5= 66-75% noru6iunx 8 = 86-99% norn6iuwx 7 = 76-85% πογμ6ιιιμχ 9 = 100 %πογμ6ιιιμχ
Ta6nwua 2 ΠρΜΜΘρ Οοθαμηθημθ HaceKOMoe nacien Ha μμπμοη η/μπη η/μπη OaKTop 10 1 0,1 10010 1 100010010 A A 9 9 3 6 0 - 0 0 0 E 23-neoKCM Φβκτορ A 9 9 9 9 0 - 9 5 0 B COOTBBTCTBMM CO ΟΠΟΟΟδΟΜ HaCTOHmero Μ3θ6ρβΤΘΗΜΗ, ΟΟΘΑΜΗΘΗΜΘ φορΜγπΒΐ (2), μοχθτ 6biTb nonyHeHO βοοοτ3ηοβπθημθμ οοθαμηθημπ φopMyπbl (ΙΥ) Ļ
rne R1 μ -OR4 μμθιοτ BbiujeyKa3aHHbie 3Η3ηθημπ,κρομθ OR4- rnflpoKcnrpynnbi, a L πβππθτοπ rpynnoM R" OC SO, rpe R" - (Ci-Cg-anKnn) Φθημπ μπμ Φθημπ, c noMOUļbK) pereHpnpyiomero areHTa, TaKoro xax onoBoruppupanKun (HanpMMep, Tpn-H-6yTMnonoBornflpnfla) b npncyTCBMM MHMLļnaTopa papuKanoB,
HanpMMep,nepMKMCM, a306MCM306yTMp0HMTpMna ΜΠΜ ΠΟΑ ΑΘΜΟΤΒΜΘΜ CBeta. 10
PeaKiļMK) mojkho τθιοκθ npoBOflMTb b cooTBeTCTByiomeM pacTBopHTene, KOTopbiii μοχθτ čtiTb BbičpaH M3 rpynnbi κθτοη3, HanpMMep, aueTOHa, npodoro 3φΜρ3, HanpuMep, flMOKcaHa, yrneBonopofla, HanpMMep, Tpnxnop6eH3ona; μπμ cnoKHoro 30npa, HanpMMep, STun-aueTaTa. Mo>kho TaiOKe ncnonb30BaTb KOMčMHauuH yKa3aHHbix pacTBopmeneii πμ6ο caMbix, πμ6ο c bopom. YKa3aHHyio peaKpmo mo>kho npoBOflMTb npM TeMnepaiype ot 0° no 200 °C, npeflnoHTMTenbHO b MmrepBane 20°-130°C.
HacTcmmee ΜβοδρβτβΗΜβ nanee npepciaBneHO cnenyK)mMMM npenapaiaMM m npMMepaMM. Bce TGMnepaTypbi πρμβθαθηη npM 0°C.
CoenMHeHMB o6o3HaHeHbi co ccbi/iKoii Ha mctok “OaKTopbi", KOTopbie npepcTaBn^iOT co6om nepeHMcneHHbie ημ>κθ οοθπμηθημα φopMyπbι (Υ) ς>Η
Φβκτορ R R1 A -H -ch(ch3)2 B -CH3 ch3 C -H -ch3 ū -H - ch2ch3
OaKTopbi A, B, C, D, E, F μοχηο nonyMHTb cnocočOM, KOTopbiii onncaH b naieHTe IOjkhom ΑφρΜΚΜ N 85/7049. ΠρΜΜθρ 1 5-φβΗ0Κ0Μ3Ι4ΘΤ0Κ0Μ-23-(4-ΜΘΤΜΠφθΗ0Κ0ΜΤΜ0Ιθρ60ΗΜΠ0Κ0Μ)
Φβκτορ A 11 LV 10314 δ-φβΗΟκαιβΜθτοκαι (Daicrop A (747 μγ) b αμχπορμθτ3ηθ (10 μπ) npn 0°C b aTM0ccļ)epe a30Ta o6pa6aTbiBa»OT πμρμαμηομ (0,81 μπ), a 33τθμ 4-ΜΘΤΜΠφθΗΜΠΧΠθρΤΜθφθρΜ3ΤΟΜ (0,75 r) B ΑΜΧΠΟρΜΘΤβΗΘ (2 ΜΠ). ΠοπγΗΘΗΗΝΜ ΤΘΜΗΜΜ paCTBOp TUļaTenbHO ΠθρβΜΘ11]ΜΒ3Κ)Τ B ΤΘΗΘΗΜΘ 15 MMHyT npn TeMnepaType 0°C, m 3aTeM b τθηθημθ eiue 22 nacoB 6β3 οχπεοκΑθΗΜΠ. rionyHeHHyio CMecb BbinneaioT b xonoflHy»o BOfly μ οοπηηομ pacTBop (paccon) m 3KCTparnpyK)T npocTbiM θφΜροΜ. Οοθαμημβιιιμθοπ οπομ npocToro 3φΜρβ npoMbieaiOT βοαομ m οοπηημμ pacTeopoM, BbicyiunBaK>T m BbinapneaioT. OcTatoK onniiļatoT χροΜθτοτρβφΜθΜ Ha κοποηκθ AByoKMCM κρθμημπ ii npenapa-tmbhom jkmakocthom χροΜβτοφβφΜθΜ c o6paTHOM φθ30Μ c nonyneHMeM Η33Β3ΗΗ0Γ0 ΟΟΘΑΜΗΘΗΜΠ (430 μπ), 6 (C CI3) COflep>KMT 3,34 (m, IH), 3,58 (m, IH), 3,97 ( g10, IH), 4,72 (c, 2H), 5,4 (m, IH), 559 (g 6, IH), m 6,9 flO 7,4 (μ, 9H), m/3 βκπιοηθθτ 728, 616, 576, 466, 464, 448, 354, 297, 247, 219 m 151. ΠριίΜβρ 2 5^eHOKCiiaueT(jKCii-23-fleoKCM Φβκτορ A Οοθαμηθημθ npMMepa 2 (350 μγ) m a3o6ncM3o6yTnpoHiiTpiina (25 μγ) b cyxoM Tonyone (20 μπ) b θΤΜΟΟφβρβ a30Ta npn TeMnepaiype 120° o6pa6oTaHO no KannnM pacTBopoM Tpn-H-6yninonoBoriiflpiifla (0,5 μπ) b cyxoM Tonyone (10 μπ). PacTBop HarpeBatOT c oāpaTHbiM χοποαμπβημκομ b τθηθημθ 90 mmh, oxna>KflaioT m BbinapMBaiOT.OcTaTOK xpoMaτoΓpaφMpyιoτ ΗΘΡΘ3 flByOKMCb ΚρβΜΗΜΠ, MCn0nb3yfl CM0Cb flMXnOpMeiaHa C aMeTOHOM (40:1) b KanecTBe pacTBopMTenn c βηχοαομ η33Β3ηηογο οοθαμηθημπ (280 μγ), δ (CDCI3(coflep>KMT 3,32 (μ,ΙΗ), 3,42 ( g10, IH), 3,57 ( μ, IH), 4,71 (c, 2H), 5,59 ( g 6, IH) m 6-8-7,4 (μ, 5H), m/3 C0flep>KMT 730, 712, 578, 560, 468, 450, 356, 314, 299, 249, 248, 221 M 151. ΠριίΜβρ 3
23-peoKCM, Φθκτορ A Οοθρμηθημθ npMMepa 2 (240 μγ) ββθαθηο b HacbiuteHHbiM pacTBop aMMOHMn b μθτθηοπθ (10 μπ) npM TeMnepaType -5°. nonyweHHbiM pacTBop nepeMeiuMBaiOT npM TeMnepaType ot 0° ao 10° b τθηθημθ 2 nacoB nepen ero BbinapMBaHMeM no cyxoro οοοτοπημπ. 0οτ3τοκ xpoMaτoΓpaφMpyιoτ nepe3 flByOKMCb ΚρβΜΗΜΠ, MCn0nb3yfl CMecb ΑΜΧΠ0ρΜΘΤ3Η3 C afleTOHOM (20:1) c nonyneHMeM Ha3BaHHoro οοθαμηθημη (180 μγ), δ (CDCI3) coflep>KMT 3,27 (μ, IH), 12 3,42 (fl 9, IH), 3,54 (m, IH), m 4,29 (mb 6, IH), m/3 COflepjKMT 596, 578, 5610, 468, 450, 356, 314, 299, 249, 248, 221 M 151. npMMep 4 23-fleoKCM-<J>aKTop A, 5-MeTnnKap6oHaT (57 μγ) 20 [ ] D +152°(c 0,6, CHCI3), λ max (E OH) 244,5 hm (ε 28200), v max (CHB Γβ) 3530 M 3460 (OH), 1740 (Kap6oHair) m 1707 cm'1( cno>KHbiii ΘφΜρ), δ ( C CI3) BKnfOHaeT 5,55 (c, IH, 3,82 (c, 3H), 3,42 (fl, J 10 Γμ, IH) H 0,69 (n, J 4 Tu, 3H) M3 23-neoKCM- Oaicropa A (90 μγ) m MeiwixnopMaTa (0,3 μπ IM-pacTBopa b αμχπορμθτβηθ). ΠρΜΜβρ 5
Ml 23-n-TonHnoKCMTHQKap6oHMnoKCM OaKTOD B Φβκτορ B (600 μγ) pacTBopunn b cyxoM πΜχπορΜβτβΗθ (5 μπ), m k 3T0My pacTBopy jqo6aBnnn cyxoii nMpuflUH (800 μγ) m n-TonnnxnopTMOHO0opMaT (750 μγ). CnycTfl 24 Haca, npn TeMnepaType OKpyxaK)ineii cpejļbi CMecb BbinHHM B 3φΜρ, H OpraHHHeCKMM paCTBOp flOBenU flO HePlTpanbHOM cpeflbl. B KonoHKy M3 CMnuKarenn (50 r) 3arpy3nnn TMOKap6oHaT b jqnxnopMeTaHe, πρμηθμ KonoHKa pa6oTana b tom xe caMOM pacTBopuTene. SmoMpOBaHue κοποΗΚΜ CMecbio flMxnopMeiaH: Θφιιρ (95:5) πο3βοπππο Bbinenmb ochobhom κομποηθητ, KOTOpbm nanee onmuancn npenapamBHO o6paTMMoii φ33θίί HP C. Ha3BaHHoe οοθπμηθημθ 6bino βμπθπθηο b βμαθ 6θομβθτηομ πθημ (417 μγ), [α] D2o + 160° (c 0,40, CHC l3), λε™ 238 hm (ε max 35,900 v max( CHB Γ3) 3470, 3530 (OH), 1705 (3φΜρ); δ ( CDCI3) BKmonan 7,18 (g 9 Γμ, 2H), 6,98 (g, 9 Tu, 2H), 5,49 ( kb. 6 H14, IH), 4,02 (g, 5 Tu, IH), 3,58 ( m, IH), 3,31 (m, IH), 3,49 (c, 3H), 2,36 (c, 3H), 1,81 (c, 3H),1,68 (g, 6, 3H), 1,61 (c, 3H), 1,53 (c, 3H), 1,00 (g, 6 Tu, 3H), H 0,82 (g, 7 Γμ, 3H), m/z=748 (M+).
(2) 23-DeoKcn OaKTOP B
TeMnepaiypa nnaBneHiin 184-186°, [oc]q22 +158° (c 0,40, CHCI3), λ^Η 238,5 (28,150) m 244,5 hm (ε max 30.650), v£ļ*> 3450 (OH) m1705 θΜ-1(οφΜρ). δ / CDCI3 / BKmoHan 4,01 (g, 6 Γμ, IH), 3,95 ( g, 6 Γμ, IH), 3,49 (c, 3H), 3,29 ( M, IH), 1,80 (c, 3H), 1,64 ( d, 6 Γμ, 3H), 1,58 (c, 3H), 1,53 (c, 3H), 0,93 (d, 7 Γμ, 3H) m 0,69 (d, 6 Γμ, 3H). ™/z=582 (M+) 13 LV 10314 M3 ΟΟΘβΜΗΘΗΜΗ (1) (350 ΜΓ) 3a ΜΟΚΠΙΟΗΘΗΜΘΜ ΤΟΓΟ, HTO 0CT3T0K χροΜ3τοΓρ3φΜροΒ3ΠΜ,ιιοποπΒ3ν3 ριίχπορμθτ3η, 33τβΜ cnepoBana CMeCb flnxnopMeTaH: 3φμιρ (95:5) no nonyHeHM?i η33Β3ηηογο οοθαμηθημη b Bupe KpncTannnHecKoro TBepporo BemecTBa npn pacTupaHun c H-neHTaHOM (no cnoco6y rīpMMepa 2). Πρμμθρ 6
Ml 5-AueTOKCii OaKTPP C K pacTBopy Oaicropa C (338 μγ) b cyxoM nupnflUHe (0,5 μπ) flo6aBnnn yKcycHbiii aHrHppufl (71 μγ). CnycTfl 20 nacoB, npn KOMHaTHoii TeMnepaiype CMecb Bbmunn b nnxnopMeTaH, a pacTBop o6pa6oTami ρο ποπ^ηθημλ HeirrpajībHoro MaTepiiana. nonyHeHHbiii τ3κμμ o6pa30M cbipoii MaTepnan onmuanu c noMoiiļbio χροΜ3τοφ3φΜΜ Hap Merck K 60, c pa3MepoM nop OKCupa κρθμημη 230-400 μθιιι (28 r). ΘΠίΟΜρΟΒβΗΜΘ ΚΟΠΟΗΚΜ paCTBOpOM ΡΜΧΠΟρΜΘΤβΗ.’ΘφΜρ (9:1) ΠρΜΒβ/ΙΟ Κ ΠΟΓ^ΗΘΗΜΚ) Η33Β3ΗΗ0Γ0 ΟΟΘΑΜΗΘΗΜΗ (210 ΜΓ), ΚΟΤΟρΟΘ 6blJ10 BblfleneHO Β BMflO TBepporo KpucTannuMecKoro BemecTBa c TeMnepaTypoii ππηβπθημη 135°, (α]ρ23 +1420(c, 0,64,CHCI3) λ8^ 244,5 hm (ε max 31,250), v max (CHBr3) 3490 (OH), 1718 (3φΜρ) m 1730 (apeTOKCM); 5 / CDCI3/ bkhk)msw 4,03 (8, 6 Γμ, IH), 3,79(5,10 Γμ, IH), 3,54 (5, 10 Tu, IH), 3,31 (m, IH), 2,14 (c, 3H), 1,74 (c, 3H), 1,66 ( 5, 7 Γμ, 3H), 1,60 (c, 3H), 1,52 ( c, 3H/, 0,98 ( 5, 6 Γμ, 3H) M 0,78 (5, 7 Γμ, 3H) m/z=626 (M+).
(2) 5-AūeTOKCH. 23-n-TonMnoKCMTMQKap6oHMnoKCM OaKTOP C (430 μγ), [ot]D23 +133°(c 0,48, CHCI3), λε^Η 237,5 (36,900), 244 (36,900) m 273 HM ( 6 max 2.400) , V max ( CHB r3) 3500 (OH), 1732 (apeiaT) m 1710'1(3φκρ). /δ CDCI^ BKnmaiOT 7,17 ( 8, 8 Γρ, 2H), 6, 99 (δ, 8,0 Γμ, 2 H), 4,04 ( 8, 6 Γμ, IH), 3,98 ( 8, 10 Γμ, IH), 3,57 ( M, IH), 3,31 (m, IH), 2,34 (c, 3H), 2, 14 (C, 3H), 1, 74 (c, 3H), 1,66 ( 8, 6 Γμ, 3H), 1,60 (c, 3H), 1,52 (c, 3H), 0,99 (8, 6 Γμ, 3H) m 0,81 (5, 7 Γμ, 3H). m/z=776(M+) H3 coeflMHeHHa (1) (500 μγ) β βμηθ ββομΒΘΤΗΟΜ neHbi. (Cnoco6 no npiiMepy (7 (1)).
(31 5-aueTOKCM. 23-neoKCn OaKTOP C (256 μγ) c TeMnepaTypoii nnaBneHHa 230°( c ρββπωκβΗΜθΜ), [<x]d231 47°(c 0,32, CHCI3); λ^Η 238,5 (28000), 244,5 hm (ε max 3030.0), v max « (CHBr3) 3440 (OH), 1730 (βμθτοκαι) m 1710 cm'1 (3φΜρ)· 6(CflCI3) βκπιοηθθτ 4,05 (δ, 5Γμ, IH), 3,57 (m, IH), 3,33 (m, IH), 2,15 (c, 3H), 1,75 (c, 3H), 1,64 (δ, 6Γμ, 3H), 14 1,59 (c, 3H), 1,53 (c, 3H), 0,99 (6, 6l“u, 3 (3H), 14 0,68 (δ, 5Γμ, 3H). ™/z=610(M+) M3 coeflMHeHMJi (2) (385 μγ) nocne Kpi4CTannu3auui4 n3 H-neHTaHa (cnocoč npuMepa 2). (41 23-ūeoKcn OaKTOD C (80 Mri [a]D 23+104°(c 0,56,CHCI3); λε™ 244,5hm (ε max 28050); v max ( CHBr3) 3540,3450 (OH), 1702 cm "1(3φΜρ). δ CflCI3 BKniOHaeT 4,28 ( m, 6l~u, IH), 3,26 (μ,ΙΗ), 1,87 (c, 3H), 1,65 (6, 7 Γρ, 3H), 1,59 (c, 3H), 1,53 (c, 3H), 0,99 (6,6 Γρ, 3H), n 0,69 (cna6o pa3peujeHHbiii ηγππβτ) 5 Γρ, 3H). m/z=568 (M+) i43 coeflMHeHun (3) (125 μγ) b βμαθ 6θομβθτηομ neHbi. Πρμμθρ 7
OaKTOP A 5-aueTaT 23-π-τοπμπτμοηοκ3ρ6οη8τ
PacTBop OaKTopa A 5-aueTaT x (4,000 r) b cyxoM ηκχπορΜβτβΗβ (50 μπ) μ b cyxoM nupMflMHe (4,9 μπ) b τοκθ a30Ta očpaāoTanu π-τοπΜπχπορτΜΟΗοφορΜβτοΜ (3,7 μπ) no Kan/iflM b τθηθημθ 10 Mi4HyT. rionyHeHHbiM τθμημμ pacTBop nepeMeujMBanii ripu κομηβτηομ TeMnepaType b τθηθημθ 45 sacoB. PacTBop pa36aBi4nn fli4xnopMeTaHOM (200 μπ), npoMbinM nocneflOBaienbHo 2 N connHon kmchotom, HacbimeHHbiM pacTBopoM 6nKap6oHaTa HaTpun, BOflOM 14 HacbiineHHbiM pacconoM (2X200 μπ), 3aTeM Bbicyuii4ni4 (cyπbφaτoM Mamnn), a pacTBopiiTenb ncnapunn m o6pa30Banacb TeMH0-3eneHan neHa. Ee BHOBb pacTBopnnn b 3Tnn-aueTaTe (200 μπ) m o6pa6oTanu aKTUBnpoBaHHbiM yrneM. nocne φκπΒτροΒθΗηπ μ oTnapuBaHun pacTBopuTenn nonyHann 6neflHO-3eneHyio neHy, KOTopyio χροΜ3τοΓρ3φΐ4ροΒ8Πΐ4 Ha nuoKcune κρβΜΗΜπ (Merck Kieselget 60, c pa3MepoM nacTnu 0,040-0,063 mm, pa3MepoM nop 230-400 Meui npn θΤΜοσφβρΗΟΜ naBneHnu, c 9monpoBaHueM CMecbio reKcaH-3TnnaueTaT (2:1) uo nonyHeHun Ha3BaHHoro οοθαμηθημπ b BMjqe δπββΗΟοκβπτοίί neHbi (3,946 r). Xmax (b 3TaHone) 245 hm (ε 34200), v max CHBr3) 3620-3340 (OH) 1731 (apeTaT), 1710 CM'1(Kap6oHnn), 5(CflC l3) BKmonaeT 6,81 (δ,6Γρ, 3H), 2,16(c,3H), 2,36(c,3H), 3,34 (μ,ΙΗ), 6,99(6, 9Γρ, 2H), 7,20 (6, 9l"u,2H).
(2) 23-neoKCn-0aKTQP A 5-aueTaT
PacTBop OaKTopa A 5-aueTaT 23-n-Toni4nTMOHOKap6oHaT (10,194 r) b cyxoM Tonyone (100 μπ) Harpenu no κμπθημπ c oOpaTHbiM xonoflnnbHMKOM b τοκβ a30Ta m o6pa6oTann α =a30-6nc-i430-6yTnpoHi4Tpi4noM (509 μγ).Πο KannnM no6aBnni4 pacTBop Tpn-H-6yTi4nTUHrpi4fla (10,25 μπ) b cyxoM Tonyone (60 μπ) b Tenemie 25 Ml4HyT, COXpaH«n Πρΐ4 9T0M KUnHMeHUe C 06paTHblM XOnOfllinbHl4KOM. CMeCb 15 LV 10314 nepeMeuiMBanM eme 25 MMHyr, 3βτθΜ οχπθρμπμ po KOMHaTHOii TeMnepaTypbi, m pacTBopMTenb ncnapunn po nonyHeHnn χθπτογο Macna.Ero pacTBOpunu b ai4eTOHMTpnne(600 μπ) m npOMbinn reKcaHOM. PacTBOpmenb ncnapMnu po ΠΟΠγΗΘΗΜΛ 6enoil neHbl, κοτοργκ) Χρ0Μ3Τ0Γρ3φΜρ0Β3ΠΜ Ha flMOKCMfle ΙφθΜΗΜΠ (Merck Kieselpet 60, c pa3MepoM nacnip 0,040-0,063 mm, m pnaMeTpoM nop 230-400 Meuj), amonpoBanM CMecbio reKcaH-amnapeTaT (4:1) po nonyHeHna Ha3BaHH0TO COepMHeHMfl (2,442 Γ), [aJD22 +1440( C 0,43 ΧΠΟροφΟρ), Xmax(B STaHone) 245,5 hm (ε 29650), v max (CHBr3) 3420-3340 (OH),1732(apeTaT), 1710 CM-1(Kap6oHMn), 5(CJļCI3) βκπιοη3ΘΤ 0,68 (g, 5Γρ, 3H), 2,16 (c,3H), 3,32 (m, IH) Πρμμθρ 8 ΓΠ 5-AueTQKCM d>aicrop Π (923 Μή [a]D21+143,9°(c 0,9,CHCI3) λε^Η 239 (28700) M 245hm(s max 31000), vmax (CHBr3) 3490(OH) 1730 Μ 1710(ΘφΜρ), 5(CflCI3) 0,81 (g, 7 Γρ,3Η), 0,99 (g, 7 Γμ, 3H), 1,00( m,7 Γρ, 3H), 1,53 (c, 3H/, 1,59 (c,3H),1,75 (c,3H),2,16 (c,3H) 3,32 (m,IH), 3,65 (m,IH), 4,04 (g,6 Γρ, IH), m 5,53 (μ, 2H). m/z=640 (M+), M3 OaKTopa fl (2,5 r) m yKcycHorc aHTMrpwpa (0,47 μπ).
I (2) 23-n-TonunoKCMTMQKap6oHnnoKCM OaKTPp D. 5-AūeTat (610 Μή [a]p21+ 132°(c 0,4,CHCI3) λε^ 238,5 (34800) w 244,5 hm (ε max 35400), vmax(CHBr3) 359 M 3560 (OH) h 1730 0Μ-1(9φιιρ); δ 0 (CflCI3) 0,81 (g, 7Γρ, 3H), 0,99 (g, 7 Γρ, 3H), 1,00 (m, 7 Η, 3H), 1,53 (c, 3H), 1,61 (c, 3H), 1,75(c,3H), 2,15 (c, 3H) 2,36 (c,3H), 3,33 (m, IH), 3,98 (g,10rp, IH), 4,04 (g, 6 Γρ, IH), 5,5-5,6 (m,2H), 6,98 (g, 9 Γρ, 2H) m 7,19 (g, 9Γρ, 2H). m/z=790 (M+), M3 5-apeTOKcn Oaicrop fl (776 μγ) μ π-τοπμπχπορτμοηο-φΟρΜβΤΒ (0,75 μπ) (cnocoā CM. ΓφΜΜβρ 7). (3^ 5-AueTOKCn. 23-neoKcn (EaKTOP Π (367 Mrt
HacTb θτογο o6pa3pa nepeKpncTannn30Bann M3 reKcaHa po nonyweHnn aHanMTMHecKM HHCToro BeipecTBa c noMombto HPLC c TeMnepaTyioii nnaBneHM* 222-224°, [a]p21 + 134°( c 0,9, CHCI3), λε^Η 245 hm (ε max 32400), v max (CHBr3) 3550, 3460(H), 1735 m 1710 0Μ-1(3φΜρ), 5(CflCI3) 0,69 (g,6 Γρ, 3H), 1,00 (g, 6Γρ, 3H), 1,00 (m, 7 Γρ, 3H), 1,53(c, 3H), 1,59(c, 3H), 1,76(c,3H), 2,14 (c, 3H), 3,31 (m, IH), 3,44 (g, 10 Γρ, IH), 4,05 (g, 6 Γρ, IH) m 5,5-5,6 (μ, 2H). m/z= 624(M+) M3 5- apeTOKCH, 23-n-TonnnoKCHTnoKap6oHnnoKCM OaKTop fl (582 μγ) (cnocoā cm. npHMep 7). (41 23-peoKCM OaKTOD Q (159 Μή 16 [α]021+ 123°( c 0,5,CHCI3), λε^χΗ244,6 ημ (ε max 28300); vmax (CHBr3) 3550 μ 3460 (ΟΗ) Μ 1705 CM-1 (9φΜρ), 6(CflCI3) 0,69 (g, 6 Γμ, 3Η), 1,00 (g, 6 Γμ, 3Η), 1,00 ( 6, 7 Γμ, 3Η), 1,53 (c, 3Η), 1,59 (c, 3Η), 1,87(c, 3Η), 3,26 (μ, ΙΗ), 3,44 (g, 10 Γμ, ΙΗ), 3,96( g, 6 Γμ, ΙΗ) μ 4,28 ( m, 6 Γμ, ΙΗ). m/z=582 (Μ+). H3 5-aMeTOKCM, 23-flnrnflpo Φβκτορ fl (231 μγ). 17 LV 10314 AHHOTALIHfl
OnncaHbi coeflMHeHMii cpopMynbi (2):
M MX COJ1M, rpe R1 πρβηοτβΒΠΛθτ MeTnnbHyK), 3TwibHyio μπμ M3onponnnbHyio rpynny; R2 npeflCTaBnaeT aTOM Bopopopa nnw rpynny OR5 ((rpe OR5 ηβπαθτοβ rnflpoKCnnbHOM rpynnoii μπμ 3aMemeHH0M ruppoKCMnbHOM rpynnoM, copep>Kameii po 25 aTOMOB ymepopa) m R3 npepcTaBnaeT aTOM Bopopopa, μπμ R2 m R3 βμθοτθ c aTOMOM yrnepopa, κ KOTopoMy ohm πρμοοθρμηακπόα, npepcTaBrmiOT rpynny C=0; m R4 npepcTaBn«eT rpynny OR5, KOTopaa μμθθτ BbiiueyKa3aHHbie 3HaHeHMfl; ripu ycnoBMM, hto Korpa R2 npepcTaermeT rnppOKCMnbHyio rpynny, OR4 npepcTaBnaeT 3aMemeHHyio rnppoKCnnbHyK) rpynny πομμμο MeTOKCunbHoii rpynnbi. yKa3aHHbie οοθρμηθημλ mo>kho πρμμθηλώ» pna 6opb6bi c HaceKOMbiMii, KnemeBupHbiMM, HeMaTopaMM vmvi ppyraMM napa3HTaMM. 18 LV 10314
OopMyna Μ3ο6ρθτθημα
Cnoco6 nonyHeHM5i ΜβκρομιικπΜΗθοκΜχ οοθρμηθημμ o6meii cļ3opMynbi 1:
(l) rpe: R1- μθτμπ, 3τμπ μπμ M3onponnn; m r3 - aTOMbi Bopopofla, OR4- rnflpoKCnrpynna, MeTOKcnrpynna, anKaHOnnKcnrpynna, MMeiomaa Ci-Ce-anbKnnHbiti φρβΓΜΘΗΤ, Heo6«3aienbHO 3aMemeHHbiii $eHOKCnrpynnoii μπμ rpynna -OCOOR5, rpe: R5-Cļ-C5 - anKnn, OTnunaiomuMCJi τθμ, hto coennHeHMe o6meii φopMyπbι 2
rpe: R1 m OR4 μμθιοτ BbiuieyKa3aHHbie 3HaHeHna, κροΜβ OR4-mnpoKcnrpynna, L- ROCSO - rpynna, rpe: R"-(Ci-C0-anKun) Φθημπ μπμ φθΗΜΠ,πορΒβρΓβίΟΤ BOccTaHOBfieHMio peucTBMeM onoBO-rMflpMfloanKuna, KaK, HanpuMep, Tpn-H-6yTnnonoBornflpnfla, b npncyTCTBmi MHuuMaTopa papMKanoB, KaK, HanpuMep, 19 β3θ6ΜΟΜ3θ6νΤΜρθΗΜΤρΜΠ3, ΜΠΜ ΠΟΑ ΑΘΜΟΤΒΜΘΜ CBeTa, Μ ΠΟ/ψΗΘΗΗΟβ ΟΟΘΑΜΗΘΗΜΘ φορΜγ/ΐΗ 1, rjqe: OR4-MeTOKcn- μπμ anKaHonnoKCM-rpynna, MMeromaa C-ļ-Cg-anKkīnbHbiii φρ3ΓΜβΗΤ, Heo6fl3aTenbHO 3aMemeHHbift φΘHOκc^lΓpyππo^ίf b cnyHae Heo6xoflMMOCTM,nepeBOflaT ero b coennHeHne φοριν^ι 1,rne: OR4-rnnpoKCnrpynna,KOTopoe b cnynae ηθο6χοαμμοοτμ ηθμοτβμθμ ranoMflaHniflpMfla KucnoTbi nepeeoflfiT b οοθαμηθημθ φοριν/^ΠΒΐ 1, rfle:OR4-OCOOR5 rpynna. LV 10314
IZGUDROJUMA REFERĀTS
MAKROCIKLISKO SAVIENOJUMU IEGŪŠANAS PAŅĒMIENS
Izgudrojums attiecas uz jaunu antibiotiku savienojumu iegūšanas paņēmienu. Tiek aprakstīti savienojumi ar formulu (I)
un to sāļi, kur R1 apzīmē metil-, etil- vai izopropilgrupu, R2 apzīmē ūdeņraža atomu vai OR5-grupu (kur OR5 ir neaizvietota vai aizvietota hidroksilgrupa, kura satur līdz 25 oglekļa atomiem) un R3 apzīmē ūdeņraža atomu, vai R2 un R3 kopā ar oglekļa atomu, pie kura viņi ir pievienoti, apzīmē >C=0 grupu; un R4 apzīmē OR5 grupu, kurai ir iepriekš norādītās nozīmes, gadījumā, ja R2 apzīmē hidroksilgrupu, tad OR4 apzīmē aizvietotu hidroksiigrupu, izņēmot metoksigrupu.
Savienojumu (I) sintēzē kā izejvielu izmanto savienojumu, kas satur 23. stāvoklī R110CSO-grupu, kur R11 -(C-j -Cg-alkil)fenii- vai fenilgrupa, reducējot to ar alkiialvas hidrīdu, piemēram, tri-n-butilalvas hidrīdu, radikāļu iniciātora, piemēram, azobisizobutironitrīla klātbūtnē, vai iedarbojoties ar gaismu.
Norādītos savienojumus var izmantot kukaiņu, ērčveidīgo, nematožu un citu parazītu apkarošanai.
Claims (1)
- LV 10314 Izgudrojuma formulakur R1 - metil-, etil- vai Izopropilgrupa, R2 un R3 - ūdeņraža atomi, OR4 - hidroksilgrupa, metoksigrupa, alkanoiloksigrupa, kura satur C-j-Cg- alkilfragmentu, kam obligāti nav jābūt aizvietotam ar fenoksigrupu, vai -OCOOR5-grupa, kur R5 ir C-j -C5-alkilgrupa, iegūšanas paņēmiens, kas atšķiras ar to, ka savienojumu ar formulu (II)kur R1 un OR4 ir tādi, kā norādīts iepriekš, Izņemot OR4- hidroksllgrupu, . L-R110CSO-grupa, kur R11 -(C-ļ-C©-alkil)f©nIl· vai fenilgrupa, reducē ar alkliaivas hldridu, piemēram, tri-n-butilalvas hldridu, radikāļu iniciātora, piemēram, azoblsi2obutironitrīla klātbūtnē, vai iedarbojoties ar gaismu, un iegūto savienojumu ar formulu (I), kur OR4-metoksi- vai alkanoiloksigrupa, kurā ir C-ļ -Cg-alkilfragments, kam nav obligāti Jābūt aizvietotam ar fenoksigrupu, nepieciešamības gadījumā pārvērš par savienojumu ar formulu (I), kur OR4-hidroksi!grupa, kuru, ja ir nepieciešams, pārvērš par formulas (I) Savienojumu, tam reaģējot ar karbonskābes halogēnanhidrīdu, kur OR4 ir OCOOR5-grupa.
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GB858510944A GB8510944D0 (en) | 1985-04-30 | 1985-04-30 | Chemical compounds |
GB868606103A GB8606103D0 (en) | 1986-03-12 | 1986-03-12 | Chemical compounds |
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LVP-93-1406A LV10314B (en) | 1985-04-30 | 1993-12-31 | Process for preparation of macrolides |
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US4457920A (en) * | 1981-09-03 | 1984-07-03 | Merck & Co., Inc. | 4a-Substituted avermectin compounds |
US4423209A (en) * | 1982-02-26 | 1983-12-27 | Merck & Co., Inc. | Processes for the interconversion of avermectin compounds |
JPS59108785A (ja) * | 1982-11-25 | 1984-06-23 | Sankyo Co Ltd | ミルベマイシン類の5−オキシム誘導体 |
JPS60126289A (ja) * | 1983-11-14 | 1985-07-05 | Sankyo Co Ltd | ミルベマイシン類の5−カ−ボネ−ト誘導体 |
PT80577B (pt) * | 1984-06-05 | 1987-09-18 | American Cyanamid Co | Processo para a producao de novos agentes macrolidos ll-f28249 uteis no tratamento de infeccoes helminticas por ectoparasitas artropodes e por acarideos |
BE903232A (fr) * | 1984-09-14 | 1986-03-13 | Glaxo Group Ltd | Composes antibiotiques et leur procede de preparation |
ES8800986A1 (es) * | 1985-07-27 | 1987-12-01 | Pfizer | Un procedimiento para la produccion de un nuevo derivado de avermectina |
-
1986
- 1986-04-28 AU AU56767/86A patent/AU596586B2/en not_active Ceased
- 1986-04-28 ES ES554444A patent/ES8802229A1/es not_active Expired
- 1986-04-28 IL IL78621A patent/IL78621A/xx not_active IP Right Cessation
- 1986-04-29 DK DK196586A patent/DK160992C/da not_active IP Right Cessation
- 1986-04-29 RU SU864027456A patent/RU2004545C1/ru active
- 1986-04-29 CA CA000507815A patent/CA1335368C/en not_active Expired - Fee Related
- 1986-04-29 SE SE8601998A patent/SE503571C2/sv not_active IP Right Cessation
- 1986-04-29 AT AT0115486A patent/AT397095B/de not_active IP Right Cessation
- 1986-04-29 LU LU86412A patent/LU86412A1/fr unknown
- 1986-04-29 KR KR1019860003297A patent/KR930011282B1/ko not_active IP Right Cessation
- 1986-04-29 IE IE112786A patent/IE59070B1/en not_active IP Right Cessation
- 1986-04-29 NL NL8601103A patent/NL193420C/nl not_active IP Right Cessation
- 1986-04-29 DE DE3614549A patent/DE3614549C2/de not_active Expired - Fee Related
- 1986-04-29 CH CH1749/86A patent/CH675124A5/de not_active IP Right Cessation
- 1986-04-29 NZ NZ215997A patent/NZ215997A/xx unknown
- 1986-04-30 GB GB08610631A patent/GB2176182B/en not_active Expired
- 1986-04-30 PT PT82485A patent/PT82485B/pt not_active IP Right Cessation
- 1986-04-30 PH PH33722A patent/PH23386A/en unknown
- 1986-04-30 HU HU861816A patent/HU200771B/hu not_active IP Right Cessation
- 1986-04-30 FR FR868606345A patent/FR2587344B1/fr not_active Expired - Fee Related
- 1986-04-30 BE BE0/216612A patent/BE904709A/fr not_active IP Right Cessation
- 1986-04-30 JP JP61098435A patent/JPH0819132B2/ja not_active Expired - Fee Related
-
1987
- 1987-04-30 ES ES557517A patent/ES8802522A1/es not_active Expired
- 1987-10-30 ES ES557774A patent/ES8900093A1/es not_active Expired
- 1987-11-10 US US07/119,347 patent/US4978675A/en not_active Expired - Lifetime
-
1988
- 1988-09-01 ES ES557851A patent/ES9000023A1/es not_active Expired
-
1993
- 1993-05-18 LV LVP-93-372A patent/LV10777B/lv unknown
- 1993-07-16 GE GEAP19931052A patent/GEP19971046B/en unknown
- 1993-12-31 LV LVP-93-1406A patent/LV10314B/lv unknown
-
1994
- 1994-12-29 GE GEAP19942319A patent/GEP19970833B/en unknown
-
1997
- 1997-02-07 GE GEAP19973574A patent/GEP20001917B/en unknown
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